CN115105463A - An ointment for repairing skin injury - Google Patents

An ointment for repairing skin injury Download PDF

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CN115105463A
CN115105463A CN202210894285.2A CN202210894285A CN115105463A CN 115105463 A CN115105463 A CN 115105463A CN 202210894285 A CN202210894285 A CN 202210894285A CN 115105463 A CN115105463 A CN 115105463A
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ointment
itaconic acid
skin
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oil
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刘蔡钺
郭猛
朱冬冬
塔娜
张盈帆
高博闻
孙一丹
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Ninth Peoples Hospital Shanghai Jiaotong University School of Medicine
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Abstract

The present invention provides an ointment for repairing skin lesions, which contains an itaconic acid derivative. The ointment provided by the invention can repair skin injuries such as burns, cut wounds, epidermal infection and the like.

Description

An ointment for repairing skin injury
Technical Field
The invention relates to the field of pharmaceutical preparations, in particular to an ointment for repairing skin injury. The invention also relates to the use of the agent for producing an ointment for repairing skin lesions.
Background
Itaconic acid of formula C 5 H 6 O 4 The structural formula is shown as formula I:
Figure BDA0003768769120000011
also known as methylene fumarate, is an organic acid produced by organisms with two carboxyl groups, which plays an important role in both the immune system of the body and industrial synthesis. Since itaconic acid has a methylene group, it is industrially important for synthesizing a polymer material. Itaconic acid was found to be produced in aspergillus as early as 30 s in the last century and was biochemically derived from the production of itaconic acid by cis-aconitic acid as an intermediate in the tricarboxylic acid cycle, catalyzed by cis-aconitic acid decarboxylase (CAD). The synthesis of itaconic acid is widely found in microorganisms, and the industry for the biosynthesis of itaconic acid is also established on the basis of this.
In recent years, it has been found that itaconic acid can be produced by various immune cells in mammals, and the metabolic enzyme catalyzing the production of itaconic acid is aconitate decarboxylase, also called immune-response gene 1(IRG 1), which is encoded by the homologous gene IRG1 of CAD. IRG1 mediates the downstream production of itaconic acid which has important functions in the body to resist pathogen infection and regulate immune response. IRG1 protein is localized to mitochondria, and during inflammation, macrophage metabolism switches to glycolysis, while mitochondrial function decreases with decreased oxygen consumption. Succinate Dehydrogenase (SDH) is one of the rate-limiting enzymes in the tricarboxylic acid cycle, which reacts with succinic acid as a substrate to produce fumaric acid and malic acid. The chemical structure of itaconic acid is close to that of succinic acid and dimethyl malonate which is a classical SDH inhibitor, so that SDH mediated succinic acid dehydrogenation reaction can be competitively inhibited, the progress of tricarboxylic acid cycle is blocked, and the accumulation of succinic acid is caused. Under the inflammatory state, the oxidative phosphorylation of cells is carried out at a high speed, and is accompanied with the increase of mitochondrial membrane potential and the generation of ROS, so that the massive production of inflammatory factors such as IL1, TNF and the like is mediated; IRG 1-mediated accumulation of itaconic acid leads to accumulation of succinic acid in macrophages, and the cellular ATP production pathway switches from the oxidative respiratory chain to the glycolytic pathway, mediating the onset of inflammation resolution.
Furthermore, itaconic acid acts on the glyoxylate cycle to exert antibacterial activity. In the long-term evolution game process of the host, the bacteria evolve a special metabolic mode represented by the glyoxylate cycle, so that the bacteria can better utilize host energy substances to maintain the survival of the bacteria, and under the condition of glucose deficiency, the glyoxylate cycle enables the bacteria to utilize a carbon source from acetyl coenzyme A such as fatty acid or cholesterol to ensure the supply of energy. acetyl-CoA in the glyoxylate cycle does not undergo decarboxylation, but isocitrate is converted to glyoxylate and succinate by isocitrate lyase (ICL). The malate synthase further catalyzes the synthesis of malate by glyoxylate and another acetyl-coenzyme molecule. The itaconic acid can be combined with an active site of the ICL, thereby generating competitive inhibition effect on a catalytic substrate succinic acid of the ICL, limiting the progress of downstream metabolic reaction and playing the anti-infection function.
Currently, topical antibiotics or hormonal drugs are commonly used to treat inflammatory diseases or wounds of the skin. Including antibiotic ointments typified by erythromycin/chloramphenicol ointments, and ointments containing glucocorticoids. Although these drugs may partially alleviate some skin disorders, they all have certain side effects. For example, glucocorticoid ointment can cause the rapid progress of tinea manuum, tinea pedis and tinea corporis caused by fungi, and cause the aggravation of folliculitis, impetigo herpetifomis and furuncle. The chronic use of antibiotic ointments for treating skin disorders also leads to a disturbance of the flora on the skin surface and to the development of resistance by Propionibacterium acnes and some purulent bacteria, which exacerbates the acne condition.
Disclosure of Invention
In view of the above-mentioned defects of the prior art, the present invention provides an ointment for repairing skin injuries, and the technical problem to be solved is to repair skin injuries such as burns, cuts, epidermal infections, etc.
In order to solve the problems, the invention adopts the technical scheme that: an ointment for repairing skin lesions, the ointment comprising an itaconic acid derivative.
Preferably, the itaconic acid derivative is configured to cross the cell membrane and convert to itaconic acid in the cell; or the itaconic acid derivative is selected from one or more of dimethyl itaconate and 4-octyl-itaconic acid.
Preferably, the skin injury comprises one or more of a burn, a cut, an epidermal infection.
Preferably, the epidermal infection is a staphylococcus aureus infection.
Preferably, the preparation method of the ointment comprises the following steps:
1) providing an aqueous phase containing itaconic acid derivatives, an oil phase, and an emulsifier;
2) mixing the water phase, the oil phase and the emulsifier to obtain the ointment.
Preferably, the molar concentration of the itaconic acid derivative in the aqueous phase is 250 mmol/L-500 mmol/L.
Preferably, the oil phase comprises a mixture of sweet almond oil and jojoba oil.
Preferably, the emulsifier is cetyl polyethylene glycol.
Preferably, the aqueous phase also contains a seaweed extract, and/or dextran, and/or sodium hyaluronate.
The invention also provides the use of an agent comprising an itaconic acid derivative for the manufacture of an ointment for the repair of skin lesions.
The invention has the beneficial effects that:
(1) the main active ingredient of the ointment is itaconic acid derivative, which does not permeate cell membrane, and the itaconic acid derivative is used in the invention, including dimethyl itaconate or 4-octyl-itaconic acid, preferably 4-octyl-itaconic acid, which can better permeate cell membrane and convert into itaconic acid in cells.
(2) The itaconic acid mediated inflammation inhibition effect has a characteristic that the effect on classical inflammatory factors such as IL6, IL1 beta and IL12 is obvious, the expression of LPS-induced I kappa B zeta and related downstream genes represented by IL6 can be greatly inhibited, and the upstream I kappa B alpha-p 65 transcription activity is not influenced. Through the mechanism, itaconic acid can inhibit activation of IkB zeta and expression of genes such as Defb4, S100a7a, Lcn2 and S100a9 at the downstream, and inflammatory injury of skin is improved.
(3) In addition to inhibiting inflammation, itaconic acid can inhibit the glyoxylate cycle and exert bacteriostatic effects.
(4) The cetyl polyethylene glycol is used as an emulsifier, and the formed paste is water-in-oil type, has both hydrophilic groups and lipophilic groups, so that the paste is more exquisite and smooth, and is easier to absorb after being applied to the skin compared with an oily emulsifier.
(5) The sweet almond oil and the jojoba oil are used as oil phase carriers instead of traditional vaseline, so that transdermal absorption can be enhanced, and the drug effect can be improved.
(6) The sodium hyaluronate has good water retention, can keep skin moist when being smeared on the skin, enables skin tissues at wound positions to keep the optimal state, accelerates the self-repairing capacity of the skin, can better protect the skin and plays a role in adjuvant therapy.
(7) The beta-glucan has certain antibacterial activity, can assist in removing oxygen free radicals to a certain extent, and can assist in healing skin.
(8) The Sargassum megatherium extract has antibacterial activity and water retention, and can be used for promoting skin healing.
(9) The production process is simple and easy to implement, low in manufacturing cost and suitable for large-scale industrial production, and simultaneously ensures that the product has better quality uniformity and stability.
(10) The itaconic acid derivative is used as a local external preparation and directly acts on the local lesion, and the itaconic acid derivative directly acts on the damaged skin mucosa, so that the local drug concentration is obviously improved, and the itaconic acid derivative has an obvious treatment effect.
The conception, the specific structure and the technical effects of the present invention will be further described with reference to the accompanying drawings to fully understand the objects, the features and the effects of the present invention.
Drawings
Fig. 1 is a schematic view of the experimental results of the therapeutic effect of the burn model in the practice 1 of the present invention. Wherein, the abscissa is the days after operation, and the ordinate is the healing rate.
Fig. 2 is a graph showing the experimental results of the treatment effect of the skin incision wound model in the embodiment 1 of the present invention. Wherein, the abscissa is the days after operation, and the ordinate is the healing rate.
Fig. 3 is a graph showing the experimental results of the therapeutic effect of the skin infection model in the embodiment 1 of the present invention. Wherein the ordinate represents the number of colonies (CFU/g) after the homogenization treatment of Log 10.
Figure 4 is a schematic representation of the transdermal efficacy assay of the modified itaconic acid ointment of example 2 of the present invention. Wherein the ordinate represents the content of itaconic acid (pg/1g tissue).
Fig. 5 is a graph showing the experimental results of two different itaconic acid derivatives in the burn model (a), the skin cut model (B) and the infection model (C) in the practice 4 of the present invention.
Detailed Description
The practice of the present invention will employ, unless otherwise indicated, conventional techniques of molecular biology, microbiology, recombinant DNA, and immunology, which are within the skill of the art. These techniques are fully described in the following documents: for example, Sambrook molecular cloning, A laboratory Manual, 2 nd edition (1989); DNA cloning, volumes I and II (D.N. Glover editor 1985); oligonucleotide synthesis (edited by m.j. gait, 1984); nucleic acid hybridization (edited by b.d. hames and s.j. higgins, 1984); protein purification: principles and practices, 2 nd edition (Springer-Verlag, n.y.), and experimental immunology handbook, volumes I-IV (d.c. well and c.c. blackwell, editors 1986). Alternatively, the procedure may be followed according to the instructions provided by the reagent manufacturer.
Unless otherwise indicated, percentages and parts are by weight. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. In addition, any methods and materials similar or equivalent to those described herein can be used in the practice of the present invention. The preferred embodiments and materials described herein are intended to be exemplary only.
Example 1
(1) Preparation of ointments containing itaconic acid derivatives
Step one, preparing a water phase. 20mmol/L of L4-hydroxyethyl piperazine ethanesulfonic acid is configured to be used as a buffer system. Weighing 4-octyl-itaconic acid and dissolving in 30mL buffer solution to make the molar concentration of 4-octyl itaconic acid 500 mmol/L. After the preparation is finished, adding phenoxyethanol to make the final concentration of phenoxyethanol be 1%.
Step two, preparing an oil phase. The corn oil is prepared by the following steps of 4: volume fraction of 1. After the preparation is finished, adding phenoxyethanol to make the final concentration of phenoxyethanol be 1%. And measuring the oil phase liquid according to 10 percent of the total volume respectively for standby.
Step three: emulsifying the ointment. The temperature of the vacuum homogenizing and emulsifying machine was set at 32 ℃ and the stirring speed was 25 rpm. After addition of the weighed oil phase liquid, cetyl polyethylene glycol (Wingchuang Deltoid ABIL EM180 water-in-oil emulsifier) was added to make the concentration of cetyl polyethylene glycol 2.5%. After mixing well, the sterilized aqueous phase was added to the emulsifier at a rate of 1.25mL/min with stirring. Continuously stirring and uniformly mixing until the paste is formed.
Step four: and (4) charging. And transferring the formed paste from the discharge hole of the homogenizing emulsifying machine to a charging bucket by using compressed air.
(2) Preparation of control ointment
Step one, preparing a water phase. 20mmol/L of L4-hydroxyethyl piperazine ethane sulfonic acid is configured as a buffer system. After the preparation is finished, adding phenoxyethanol to make the final concentration of phenoxyethanol be 1%.
Step two, preparing an oil phase. The corn oil is prepared from the following components in percentage by weight: volume fraction of 1. After the preparation is finished, adding phenoxyethanol to make the final concentration of phenoxyethanol be 1%. And measuring the oil phase liquid according to 10 percent of the total volume respectively for standby.
Step three: emulsifying the paste. The temperature of the vacuum homogenizing and emulsifying machine was set at 32 ℃ and the stirring speed was 25 rpm. After the weighed amount of oil phase liquid was added, cetyl polyethylene glycol (water-in-oil emulsifier) was added so that the concentration of cetyl polyethylene glycol was 2.5%. After mixing well, the sterilized aqueous phase was added to the emulsifier at a rate of 1.25mL/min with stirring. Continuously stirring and uniformly mixing until the paste is formed.
Step four: and (4) charging. And transferring the formed paste from the discharge hole of the homogenizing and emulsifying machine to a charging bucket by utilizing compressed air.
(3) Therapeutic Effect of burn model
The experimental method comprises the following steps: healthy C57 mice, 6 weeks old, were used and their back hair was removed with depilatory cream and thoroughly disinfected with iodophor. The model is established by using a point-shaped warm-heat scalding method, the animal is anesthetized, the back of the animal is fixed below a scalding plate, and the bottom end of a point-shaped scalding device clings to a simulated scalding area of the experimental animal to scald by virtue of the dead weight of the scalding device. The punctiform scald apparatus is a hollow red copper cylinder with the height of 11.6cm, the diameter of the bottom end of 1.5cm and the self weight of 0.5kg, a water inlet pipe is connected with a constant temperature water bath kettle, constant temperature water (80 ℃ plus or minus 1 ℃) enters the cylinder and flows out from a side pipe without circulating, and the outside of the cylinder is wrapped with asbestos to prevent heat dissipation. Treatment of the epidermis for 20s at 80 ℃ resulted in a III degree burn. Mice were randomly divided into two groups of 5 mice each. The first group (itaconic acid group) was treated with the ointment containing itaconic acid derivative prepared above, and the second group (control group) was treated with the control ointment prepared above. The ointment (2 days/time) was topically applied to the wound site of the mice, respectively, followed by covering the wound with a wound dressing. The dressing change is carried out every 2 days after the operation, the wound parts of the mice are shot by a digital camera, and the area of the wound parts is zoomed and calculated by ImageJ.
The results of 5 wound closure rates per group were averaged for the healing rate ([ wound area (day of operation) -wound area (day of measurement) ])/wound area (day of operation) × 100%.
The results of the experiment are shown in FIG. 1. The results show that the ointment containing the itaconic acid derivative can significantly improve the healing rate of the wound compared to the control ointment. The itaconic acid group showed a significantly accelerated healing effect starting on day 7 after burn injury. On day 12 post-burn, the itaconic acid group had more than 80% wound closure, significantly higher than the control group.
(4) Therapeutic effect of skin cutting wound model
The experimental method comprises the following steps: after the hair on the back of the mice was removed with depilatory cream using C57, which was 6 weeks old, it was thoroughly disinfected with iodophor. Full thickness (D ═ 5mm) excisional skin wounds were created on the dorsal area of the mice. Mice were randomly divided into two groups of 5 mice each. The first group (itaconic acid group) was treated with the ointment containing itaconic acid derivative prepared above, and the second group (control group) was treated with the control ointment prepared above. The ointment (2 days/time) was topically applied to the wound site of the mice, respectively, followed by covering the wound with a wound dressing. The dressing change was performed every 2 days after the operation, and the wound site of the mouse was photographed with a digital camera, and the area of the wound site was scaled and calculated using ImageJ.
The results were averaged for 5 wound closure rates per group ([ wound area (day of operation) -wound area (day of measurement) ])/wound area (day of operation) × 100%.
The results of the experiment are shown in FIG. 2. The results show that the ointment containing the itaconic acid derivative can significantly improve the healing rate of the wound compared to the control ointment. The itaconic acid group showed a significantly accelerated healing effect starting on day 9 after surgery. On day 19 post-surgery, the itaconic acid group wounds were completely closed, significantly higher than the control group.
(5) Therapeutic Effect of skin infection model
Animal modeling: after the hair on the back of the mouse was completely removed with depilatory cream using C57 at 6 weeks of age and thoroughly sterilized with iodophor, the mouse was wiped with a cotton ball of sterile physiological saline for 5 times to remove residual iodophor. The method comprises the steps of using a TAP method for modeling, carrying out intraperitoneal injection of pentobarbital for anesthesia before modeling, tightly adhering a medical adhesive tape to the skin of a depilatory part with basically the same force, continuously pressing for 7 times by fingers, then tearing off, replacing the adhesive tape in each adhering-tearing-off process, continuously removing the horny layer for multiple times, calibrating the damage degree of a skin barrier by measuring TEWL, and needing the TEWL of a modeled mouse to be more than 70g/m2 & h.
Preparing bacterial liquid and infecting: staphylococcus aureus was inoculated into M-H broth containing 1.5% serum and cultured under shaking for 1H, and the amount of the culture was adjusted to 7.5X 10 6 CFU/mL. Inoculating corresponding bacterial liquid at the TAP skin lesion; packaging 10 μ L of each with gauze; and booster infection was performed after 2h, 20. mu.L each, thereby obtaining a Staphylococcus aureus skin infection mouse model.
Local therapeutic administration: staphylococcus aureus skin infected mice were randomly divided into two groups of 5 mice each. The first group (itaconic acid group) was treated with the ointment containing itaconic acid derivative prepared above, and the second group (control group) was treated with the control ointment prepared above, and treatment was given to the local infection focus. The first dose was 3 hours post-surgery and the second dose was 6 hours later. Each group was then administered twice daily at 1mg ointment per time to the damaged site.
Inspecting the viable bacteria amount of the infected wound surface: the mice are sacrificed on the 3 rd day after infection, the skin of the infected wound is taken, weighed, homogenized, diluted properly and smeared on a mannitol sodium chloride agar culture medium, and colony counting is carried out after 18-24h of culture.
Results were averaged for the number of 5 colonies per group.
The results of the experiment are shown in FIG. 3. The result shows that compared with the control ointment, the ointment containing the itaconic acid derivative can obviously inhibit the growth of staphylococcus aureus on the skin wound.
Example 2
(1) Preparation of ointments containing itaconic acid derivatives
Step one, preparing a water phase. 20mmol/L of L4-hydroxyethyl piperazine ethanesulfonic acid is configured to be used as a buffer system. Weighing 4-octyl-itaconic acid and dissolving in 30mL buffer solution to make the molar concentration of 4-octyl itaconic acid 500 mmol/L. After the solution was sufficiently dissolved, 15mL of the seaweed extract, 20mL of 2% beta-glucan and 20mL of 5% sodium hyaluronate were added thereto. After the preparation is finished, adding phenoxyethanol to make the final concentration of phenoxyethanol be 1%.
Step two, preparing an oil phase. Sweet almond oil (obtained by pressing sweet almond kernels) and Jojoba oil (also known as Jojoba oil) were mixed in a ratio of 4: volume fraction of 1. After the preparation is finished, adding phenoxyethanol to make the final concentration of phenoxyethanol be 1%. And measuring the oil phase liquid according to 10 percent of the total volume for standby.
Step three: emulsifying the paste. The temperature of the vacuum homogenizing and emulsifying machine was set at 32 ℃ and the stirring speed was 25 rpm. After the weighed amount of oil phase liquid was added, cetyl polyethylene glycol (water-in-oil emulsifier) was added so that the concentration of cetyl polyethylene glycol was 2.5%. After mixing well, the sterilized aqueous phase was added to the emulsifier at a rate of 1.25mL/min with stirring. Continuously stirring and uniformly mixing until the paste is formed.
Step four: and (4) charging. And transferring the formed paste from the discharge hole of the homogenizing and emulsifying machine to a charging bucket by utilizing compressed air.
(2) Research on transdermal effect of improved cream
Healthy C57 mice, 6 weeks old, were used and randomized into three groups of 5 mice each. The first group (control group) was subjected to a skin permeation test using the control ointment prepared in example 1, the second group (itaconic acid ointment group) was subjected to a skin permeation test using the itaconic acid derivative-containing ointment prepared in example 1, and the second group (modified ointment group) was subjected to a skin permeation test using the itaconic acid derivative-containing ointment prepared in this example. The method of the transdermal effect test is as follows.
An equal amount of the ointment (0.5g) was applied to the back of a nude mouse, and after 2 hours, the applied surface was wiped with a wet cotton ball, skin tissues with similar areas were cut, a dermal layer tissue was scraped, and the content of itaconic acid was quantified using liquid chromatography-mass spectrometry.
The results for each group of 5 contents were averaged.
The results show that the itaconic acid derivative ointment (modified ointment set) prepared in this example can effectively increase the itaconic acid concentration in the dermis, and has better transdermal effect (fig. 4).
Example 3
(1) Preparation of ointments containing itaconic acid derivatives
Step one, preparing a water phase. 10mmol/L of L4-hydroxyethyl piperazine ethane sulfonic acid is configured as a buffer system. Weighing 4-octyl-itaconic acid and dissolving in 30mL buffer solution to make the molar concentration of 4-octyl itaconic acid 250 mmol/L. After the solution was sufficiently dissolved, 10mL of the seaweed extract, 10mL of 2% beta-glucan and 10mL of 5% sodium hyaluronate were added thereto. After the preparation is finished, adding phenoxyethanol to make the final concentration of phenoxyethanol be 1%.
Step two, preparing an oil phase. Sweet almond oil (obtained by pressing sweet almond kernels) and Jojoba oil (also known as Jojoba oil) were mixed in a ratio of 3: volume fraction of 1. After the preparation is finished, adding phenoxyethanol to make the final concentration of phenoxyethanol be 1%. And measuring the oil phase liquid according to 8 percent of the total volume respectively for standby.
Step three: emulsifying the paste. The temperature of the vacuum homogenizing and emulsifying machine was set at 32 ℃ and the stirring speed was 25 rpm. After addition of the weighed oil phase liquid, cetyl polyethylene glycol (Wingchuang Deltoid ABIL EM180 water-in-oil emulsifier) was added to make the concentration of cetyl polyethylene glycol 2%. After mixing well, the sterilized aqueous phase was added to the emulsifier at a rate of 1.25mL/min with stirring. Continuously stirring and uniformly mixing until the paste is formed.
Step four: and (4) charging. And transferring the formed paste from the discharge hole of the homogenizing and emulsifying machine to a charging bucket by utilizing compressed air.
(2) Therapeutic Effect of skin Damage model
The ointment containing itaconic acid derivatives prepared above was used to treat skin burn models, skin cut models, and skin infection models, and the preparation method and treatment method of the models were the same as those of example 1.
The results showed that the ointments containing itaconic acid derivatives in this example had substantially the same therapeutic effect on the skin burn model, skin cut model, and skin infection model, compared to the ointments containing itaconic acid derivatives in example 2.
Example 4
(1) Preparation of ointments containing itaconic acid derivatives
Step one, preparing a water phase. 20mmol/L of L4-hydroxyethyl piperazine ethanesulfonic acid is configured to be used as a buffer system. An equimolar amount of dimethyl itaconate (relative to 4-octyl-itaconic acid in example 1) was weighed and dissolved in 30mL of buffer to give a final itaconic acid derivative concentration of 500 mmol/L. After the solution was sufficiently dissolved, 15mL of the seaweed extract, 20mL of 2% beta-glucan and 20mL of 5% sodium hyaluronate were added thereto. After the preparation is finished, adding phenoxyethanol to make the final concentration of phenoxyethanol be 1%.
Step two, preparing an oil phase. Sweet almond oil (obtained by pressing sweet almond kernels) and Jojoba oil (also known as Jojoba oil) were mixed in a ratio of 4: volume fraction of 1. After the preparation is finished, adding phenoxyethanol to make the final concentration of phenoxyethanol be 1%. And measuring the oil phase liquid according to 10 percent of the total volume respectively for standby.
Step three: emulsifying the paste. The temperature of the vacuum homogenizing and emulsifying machine was set at 32 ℃ and the stirring speed was 25 rpm. After the weighed oil phase liquid was added, cetyl polyethylene glycol () was added so that the concentration of cetyl polyethylene glycol was 2.5%. After mixing well, the sterilized aqueous phase was added to the emulsifier at a rate of 1.25mL/min with stirring. Continuously stirring and uniformly mixing until the paste is formed.
Step four: and (4) charging. And transferring the formed paste from the discharge hole of the homogenizing and emulsifying machine to a charging bucket by utilizing compressed air.
(2) Therapeutic Effect of skin Damage model
The ointment containing itaconic acid derivatives prepared above was used to treat skin burn models, skin cut models, and skin infection models, and the preparation method and treatment method of the models were the same as those of example 1.
The results showed that the ointment containing itaconic acid derivative dimethyl itaconate in this example had substantially the same therapeutic effect on the skin burn model, skin cut model, and skin infection model, as compared to the ointment containing itaconic acid derivative in example 2 (fig. 5).
The foregoing detailed description of the preferred embodiments of the invention has been presented. It should be understood that numerous modifications and variations could be devised by those skilled in the art in light of the present teachings without departing from the inventive concepts. Therefore, the technical solutions available to those skilled in the art through logic analysis, reasoning and limited experiments based on the prior art according to the concept of the present invention should be within the scope of protection defined by the claims.

Claims (10)

1. An ointment for repairing skin lesions, comprising an itaconic acid derivative.
2. The ointment of claim 1, wherein the itaconic acid derivative is configured to cross cell membranes and convert to itaconic acid in a cell; or the itaconic acid derivative is selected from one or more of dimethyl itaconate and 4-octyl-itaconic acid.
3. The ointment of claim 1, wherein the skin injury comprises one or more of a burn, a cut, and an epidermal infection.
4. The ointment of claim 3, wherein the epidermal infection is a Staphylococcus aureus infection.
5. The ointment of claim 1, wherein said ointment is prepared by a process comprising:
1) providing an aqueous phase containing itaconic acid derivatives, an oil phase, and an emulsifier;
2) mixing the water phase, the oil phase and the emulsifier to obtain the ointment.
6. The ointment of claim 5 wherein the molar concentration of itaconic acid derivative in the aqueous phase is 250mmol/L to 500 mmol/L.
7. An ointment according to claim 5 wherein the oily phase comprises a mixture of sweet almond oil and jojoba oil.
8. The ointment of claim 5, wherein the emulsifier is cetyl polyethylene glycol.
9. The ointment of claim 5, wherein the aqueous phase further comprises seaweed extract, and/or dextran, and/or sodium hyaluronate.
10. Use of an agent for the preparation of an ointment for the repair of skin lesions, characterized in that the agent comprises an itaconic acid derivative.
CN202210894285.2A 2022-07-27 2022-07-27 An ointment for repairing skin injury Pending CN115105463A (en)

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014151439A1 (en) * 2013-03-15 2014-09-25 Lubrizol Advanced Materials, Inc. Itaconic acid polymers for oral care applications
US20150086986A1 (en) * 2011-09-23 2015-03-26 Universite Du Luxembourg Method to predict the presence of inflammation or itaconic acid, irg1 and/or protein irg1 in a subject and pharmaceutical composition for treating or preventing inflammation
US20200375929A1 (en) * 2017-08-14 2020-12-03 Washington University Methods and compositions for the treatment of diseases associated with cancer, inflammation, or immune response
CN114028375A (en) * 2021-12-17 2022-02-11 徐州医科大学 Application of dimethyl itaconate in preparation of medicine for preventing and/or treating obesity-induced intestinal micro-ecological disorder
CN114557993A (en) * 2022-03-22 2022-05-31 中南大学湘雅三医院 Application of 4-octyl itaconate in preparation of injection preparation before pancreas islet extraction

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20150086986A1 (en) * 2011-09-23 2015-03-26 Universite Du Luxembourg Method to predict the presence of inflammation or itaconic acid, irg1 and/or protein irg1 in a subject and pharmaceutical composition for treating or preventing inflammation
WO2014151439A1 (en) * 2013-03-15 2014-09-25 Lubrizol Advanced Materials, Inc. Itaconic acid polymers for oral care applications
US20200375929A1 (en) * 2017-08-14 2020-12-03 Washington University Methods and compositions for the treatment of diseases associated with cancer, inflammation, or immune response
CN114028375A (en) * 2021-12-17 2022-02-11 徐州医科大学 Application of dimethyl itaconate in preparation of medicine for preventing and/or treating obesity-induced intestinal micro-ecological disorder
CN114557993A (en) * 2022-03-22 2022-05-31 中南大学湘雅三医院 Application of 4-octyl itaconate in preparation of injection preparation before pancreas islet extraction

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